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Evaluation of the anticancer and anti‐metastasis effects of novel synthetic sodium channel blockers in prostate cancer cells in vitro and in vivo
Author(s) -
Wang Jiajia,
Lu Zongliang,
Wu Changpeng,
Li Yanwu,
Kong Ya,
Zhou Rui,
Shi Kun,
Guo Jing,
Li Na,
Liu Jie,
Song Wei,
Wang He,
Zhu Mingxing,
Xu Hongxia
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23711
Subject(s) - du145 , lncap , viability assay , cell cycle , cell growth , mtt assay , cancer cell , cancer research , apoptosis , prostate cancer , annexin , chemistry , cyclin dependent kinase 1 , cancer , biology , medicine , biochemistry
Background Voltage‐gated sodium channels (VGSCs) are involved in several cellular processes related to cancer cell growth and metastasis, including adhesion, proliferation, apoptosis, migration, and invasion. We here in investigated the effects of S0154 and S0161, two novel synthetic sodium channel blockers (SCBs), on human prostate cancer cells (PC3, DU145, and LnCaP) and a prostate cancer xenograft model. Methods The MTT assay was used to assess the anticancer effects of SCBs in PC3, DU145, and LnCaP cells. Sodium indicator and glucose uptake assays were used to determine the effects of S0154 and S0161 in PC3 cells. The impact of these SCBs on the proliferation, cell cycle, apoptosis, migration, and invasion of PC3 cells were determined using a CFDA‐SE cell proliferation assay, cell cycle assay, annexin V‐FITC apoptosis assay, transwell cell invasion assay, and wound‐healing assay, respectively. The protein expression levels of Nav1.6, Nav1.7, CDK1, cyclin B1, MMP2, MMP9 in PC3 cells were analysis by Western blotting. The in vivo anticancer activity was evaluated using a PC3 xenograft model in nude mice. Results S0154 and S0161 both showed anticancer and anti‐metastatic effects against prostate cancer cells and significantly inhibited cell viability, with IC 50 values in the range of 10.51‐26.60 μmol/L (S0154) and 5.07‐11.92 μmol/L (S0161). Both compounds also increased the intracellular level of sodium, inhibited the protein expression of two α subunits of VGSCs (Nav1.6 and Nav1.7), and caused G2/M phase cell cycle arrest, with no or minor effects on cell apoptosis. Concentrations of 5 and 10 μmol/L of S0154 and S0161 significantly decreased the glucose uptake of PC3 cells. The compounds also inhibited the proliferation of PC3 cells and decreased their invasion in transwell assays. Furthermore, S0161 exerted antitumor activity in an in vivo PC3 xenograft model in nude mice, inhibiting the growth of the tumors by about 51% compared to the control group. Conclusions These results suggest that S0154 and S0161 have anticancer and anti‐metastasis effects in prostate cancer cells both in vitro and in vivo, supporting their further development as potential therapeutic agents for prostate cancer.